U.S. patent number 5,736,165 [Application Number 08/277,718] was granted by the patent office on 1998-04-07 for in-the-eye use of chlorine dioxide-containing compositions.
This patent grant is currently assigned to Allergan. Invention is credited to Claude B. Anger, Anthony J. Dziabo, Paul S. Ripley.
United States Patent |
5,736,165 |
Ripley , et al. |
April 7, 1998 |
In-the-eye use of chlorine dioxide-containing compositions
Abstract
Disclosed are in-the-eye uses of chlorine dioxide-containing
compositions as effective ophthalmic antiseptics and as effective
ophthalmic surgical irrigants. Surprisingly low concentrations of
chlorine dioxide are effective in such applications. In addition,
the presently useful compositions are ophthalmically
acceptable.
Inventors: |
Ripley; Paul S. (Irvine,
CA), Dziabo; Anthony J. (Lake Forest, CA), Anger; Claude
B. (Long Beach, CA) |
Assignee: |
Allergan (Waco, TX)
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Family
ID: |
23062075 |
Appl.
No.: |
08/277,718 |
Filed: |
July 20, 1994 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
Issue Date |
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66746 |
May 25, 1993 |
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Current U.S.
Class: |
424/661; 424/662;
424/665; 424/615; 514/914; 422/37; 514/912; 424/613 |
Current CPC
Class: |
A61K
33/40 (20130101); A61K 39/40 (20130101); Y10S
514/912 (20130101); Y10S 514/914 (20130101) |
Current International
Class: |
A61K
33/40 (20060101); A61K 39/40 (20060101); A61K
033/20 (); A61K 033/40 (); A01N 059/00 () |
Field of
Search: |
;424/661,662,663,664,665,613,615 ;422/37 ;514/912,914 |
References Cited
[Referenced By]
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483-486(1982). .
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|
Primary Examiner: Pak; John
Attorney, Agent or Firm: Uxa; Frank J.
Parent Case Text
RELATED APPLICATIONS
This application is a continuation-in-part of application Ser. No.
08/066,746, filed May 25, 1993, now abandoned, which application is
incorporated in its entirety herein by reference.
Claims
What is claimed is:
1. A method of caring for a mammalian eye comprising:
applying directly to a mammalian eye an effective, ophthalmically
acceptable amount of a composition which includes chlorine dioxide
in an amount effective as an antiseptic in said eye, said amount of
chlorine dioxide being less than about 50 ppm by weight of said
composition.
2. The method of claim 1 wherein said composition is in the form of
an aqueous liquid medium.
3. The method of claim 2 wherein said composition has a pH in the
range of about 6 to about 10.
4. The method of claim 3 wherein said composition is substantially
isotonic.
5. The method of claim 1 which further comprises producing said
composition from a precursor composition including a chlorine
dioxide precursor component.
6. The method of claim 5 wherein said producing step occurs
directly prior to said applying step.
7. The method of claim 5 wherein said composition is substantially
free of any component or residue thereof used to promote the
production of chlorine dioxide from said chlorine dioxide precursor
component.
8. The method of claim 1 wherein said composition includes an
amount of chlorine dioxide in the range of about 0.2 to about 15
ppm by weight.
9. The method of claim 1 wherein said composition includes an
amount of chlorine dioxide in the range of about 0.5 to about 10
ppm by weight.
10. The method of claim 1 wherein said mammalian eye has a
microbial infection and said applying is effective in treating said
microbial infection.
11. The method of claim 1 wherein said applying comprises direct
topical installation of said composition into said mammalian
eye.
12. The method of claim 1 wherein said applying is repeated.
13. A method of irrigating ocular tissue during ophthalmic surgery
comprising:
administering directly to an area of a mammalian eye undergoing a
surgical procedure an amount of a composition effective to irrigate
said area, said composition being ophthalmically acceptable and
including chlorine dioxide in an antimicrobially effective
amount.
14. The method of claim 13 wherein said administering is effective
in disinfecting said area.
15. The method of claim 13 wherein said composition is an aqueous
liquid medium.
16. The method of claim 15 wherein said composition has a pH in the
range of about 6 to about 10.
17. The method of claim 16 wherein said composition is
substantially isotonic.
18. The method of claim 13 which further comprises producing said
composition from a precursor composition including a chlorine
dioxide precursor component.
19. The method of claim 18 wherein said producing step occurs
directly prior to said applying step.
20. The method of claim 18 wherein said composition is
substantially free of any component or residue thereof used to
promote the production of chlorine dioxide from said chlorine
dioxide precursor component.
21. The method of claim 13 wherein said composition includes an
amount of chlorine dioxide in the range of about 0.05 to about 10
ppm by weight.
22. The method of claim 13 wherein said composition includes an
amount of chlorine dioxide in the range of about 0.1 to about 5 ppm
by weight.
Description
BACKGROUND OF THE INVENTION
The present invention relates to new uses of chlorine
dioxide-containing compositions. More particularly, the invention
relates to uses of compositions including effective amounts of
chlorine dioxide in the eye to obtain surprising benefits without
detrimentally affecting the eye.
The use of chlorine dioxide dissolved in an aqueous liquid medium
to disinfect contact lenses has previously been suggested. See, for
example, the following U.S. Patents: U.S. Pat. Nos. 4,997,626;
5,279,673; 5,078,908; and 5,129,999, each of which is incorporated
in its entirety herein by reference. After disinfection, the
contact lenses are removed from the liquid medium and placed in the
eye for safe and comfortable wear. Alternately, the disinfected
contact lens can be rinsed free of residual chlorine
dioxide-containing liquid medium and, then, placed in the eye for
safe and comfortable wear. Thus, although small, residual amounts
chlorine dioxide have been found to be relatively innocuous in the
eye, no suggestion has been made regarding using effective amounts
of chlorine dioxide in the eye.
Various compositions have been suggested for use in the eye to
produce effects while in the eye. For example, ophthalmic
antiseptics have been used to treat a variety of ocular infections,
for example, bacterial conjunctivitis and the like. One problem
that has existed with regard to prior ophthalmic antiseptic
compositions is that the effective ingredients tend to lose potency
or effectiveness over a period of time. Thus, such compositions
have a relatively short shelf life before becoming ineffective.
Higher concentrations of the effective ingredient or ingredients
can be included in such compositions to compensate for the gradual
loss of potency. However, such higher concentrations of active
ingredients tend to have adverse effects on the eye being treated.
Clearly it would be advantageous to provide ophthalmic antiseptic
compositions which have relatively long shelf lives and/or include
active ingredients which are effective at concentrations which do
not adversely affect the eye.
Another in-the-eye use of compositions has been as surgical
irrigants to effectively irrigate an ocular surgical area. Because
the ocular surgical area is being subjected to surgical trauma, it
is important that the irrigant be effective without causing any
additional harm to the eye. Prior art compositions have, for the
most part, been focused on providing a sterile liquid, such as a
buffered saline solution, as an irrigant. Although sterile buffered
saline does not contaminate the ocular surgical area, it is
relatively ineffective in removing or reducing microbial
contamination that may be present from other sources. It would be
advantageous to provide ocular surgical irrigants which are not
only effective as irrigants but also are antimicrobially effective
in the ocular surgical area.
SUMMARY OF THE INVENTION
New uses for chlorine dioxide-containing compositions in the eye
have been discovered. Surprisingly, it has been found that
relatively low concentrations of chlorine dioxide are sufficient to
be effective ophthalmic antiseptics and to be antimicrobially
active in ocular surgical areas. Compositions, which include such
effective amounts of chlorine dioxide, have been found to be
ophthalmically acceptable for in-the-eye use. The present invention
is easy and straightforward to practice. For example, the invention
can be practiced using techniques used in employing prior art
ophthalmic antiseptics and ocular surgical irrigants. Little or no
additional cost is involved in practicing the present invention
relative to using conventional ophthalmic antiseptics and ocular
surgical irrigants. The chlorine dioxide-containing compositions
useful in the present methods can be formed from stable precursor
compositions very shortly (directly) prior to use. Such precursor
compositions have relatively long shelf lives, and produce chlorine
dioxide-containing compositions having reliable and reproducible
chlorine dioxide concentrations which are effective as ophthalmic
antiseptics and ocular surgical irrigants, and are ophthalmically
acceptable.
As used herein, the term "ophthalmically acceptable" refers to any
material or combination of materials which, in the concentrations
employed, has no undue detrimental effect on the eye or the ocular
tissue with which it comes in contact.
In one broad aspect of the present invention, methods for caring
for a mammalian eye are provided. These caring methods comprise
administering to a mammalian eye, preferably a human eye, an
effective amount of a composition, preferably in the form of an
aqueous liquid medium, which includes chlorine dioxide in an amount
effective as an antiseptic in the eye. The amount of chlorine
dioxide is less than about 50 or about 25 parts per million (ppm)
by weight of the composition. Such administering is particularly
effective where the eye has a microbial infection, such as
bacterial conjunctivitis and/or other microbial infection, since
such administering is effective in treating, preferably reducing or
even eliminating, the microbial infection. The presently useful
compositions preferably have a pH in the range of about 6 to about
10 and/or are substantially isotonic.
In another broad aspect of the present invention, methods of
irrigating ocular tissue during ophthalmic surgery are provided.
Such irrigating methods comprise administering to an area of a
mammalian eye, preferably a human eye, undergoing a surgical
procedure an amount of a composition effective to irrigate the
area. This composition is ophthalmically acceptable and includes
chlorine dioxide in an antimicrobially effective amount.
Preferably, the administering is effective in disinfecting the
ocular surgical area, that is the area of the eye coming in contact
with the irrigating composition. Preferably the presently useful
compositions include chlorine dioxide in an effective disinfecting
amount. The presently useful irrigating compositions are preferably
present in the form of an aqueous liquid medium, and more
preferably have a pH in the range of about 6 to about 10 and/or are
substantially isotonic.
These and other aspects and advantages of the present invention
will become apparent hereinafter, particularly when considered in
conjunction with the examples and claims.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is directed to new in-the-eye uses of
compositions including effective amounts of chlorine dioxide. Such
compositions have been found to be effective as ophthalmic
antiseptics or ophthalmic surgical irrigants while having no
adverse effects on the ocular tissue coming into contact with the
compositions.
Methods for caring for a mammalian, preferably human, eye are
provided employing a chlorine dioxide-containing composition as an
effective antiseptic. As used herein, the term "antiseptic" refers
to a material or combination of materials which is effective, in
the concentration employed, to kill microorganisms, for example,
bacteria, with which it comes in contact. Specifically with regard
to an ophthalmic antiseptic, such material or combination of
materials is effective to at least reduce, or even eliminate, an
existing microbial, for example, bacterial, infection in an eye
with which it comes in contact and/or to prevent microbial
infections in an eye with which it comes in contact.
In general, the present eye caring methods comprise administering
to a mammalian eye an effective amount of a composition which
includes chlorine dioxide in an amount effective as an antiseptic
in the eye. The amount of chlorine dioxide is less than about 50 or
less than about 25 parts per million (ppm) by weight of the
composition. Such administering is particularly effective where the
eye is susceptible to or has a microbial infection, such as
bacterial conjunctivitis, since such administering is particularly
effective in preventing or treating, preferably reducing or even
eliminating, such microbial infections.
The presently useful antiseptic compositions may be in any suitable
form, such as a cream, lotion, ointment, liquid and the like, and
are preferably administered directly to the eye being cared for.
Such administering can, and preferably does, include periodic or
repeated applications of the chlorine dioxide-containing
composition to the eye. Such periodic applications to eyes which
are susceptible to, but do not have, microbial infections have been
found to effectively prevent microbial infections from occurring in
such eyes. In the event, as is preferred, the presently useful
compositions are in the form of a liquid medium, the administering
preferably comprises applying one or more drops of the liquid
medium directly to the mammalian eye.
The amount of chlorine dioxide present in the presently useful
antiseptic compositions is effective to act as an antiseptic in the
eye. The amount of chlorine dioxide is preferably in the range of
about 0.2 to about 15, more preferably about 0.5 to about 10 and
still more preferably about 1 to about 5, ppm by weight of the
composition. It has surprisingly been found that compositions which
have such reduced concentrations of chlorine dioxide are very
effective as antiseptics in the eye.
The presently useful antiseptic compositions preferably have a pH
in the range of about 6 to about 10 and/or are substantially
isotonic. Effective amounts of buffer components and/or tonicity
adjusting components may be included to provide that such
compositions have the desired pH values and/or tonicities. Buffer
components and tonicity adjusting components useful in other
ophthalmic-related compositions may be employed in the presently
useful compositions. In addition, one or more other components,
such as those known to be useful in ophthalmic-related
compositions, may be included in the presently useful compositions
in amounts effective to provide such compositions with one or more
desired properties. For example, the form of the presently useful
compositions may be obtained and/or maintained using one or more of
such other components, as fillers, emollients, surfactants and the
like.
Methods of irrigating ocular tissue during ophthalmic surgery are
provided. In general, such irrigating methods comprise
administering to an area of a mammalian eye undergoing a surgical
procedure an amount of a composition effective to irrigate the
area. Irrigation of an ocular area during ophthalmic surgery is
often desirable, or even necessary, for example, to remove detached
tissue, fluids and/or other debris from the area and/or to allow
the surgeon to have an unobstructed view of the surgical area
and/or to otherwise facilitate the surgical procedure. The
presently useful irrigants may be employed to facilitate various
ocular surgical procedures, for example, the removal and/or
replacement of a natural lens in the eye, a vitrectomy, a corneal
transplant and the like.
The presently useful ophthalmic surgical irrigant compositions are
ophthalmically acceptable and include chlorine dioxide in an
antimicrobially effective amount. Preferably, the above-noted
administering step is effective in disinfecting the ocular surgical
area, that is the area of the eye coming in contact with the
irrigating composition. Thus, preferably the presently useful
compositions include chlorine dioxide in an effective disinfecting
amount. As used herein, a disinfecting amount of chlorine dioxide
is such amount as to reduce the microbial burden or load by one log
order in three hours or less, preferably in one hour or less, more
preferably in ten minutes or less.
The presently useful irrigating compositions are preferably present
in the form of a liquid medium, more preferably an aqueous liquid
medium, and still more preferably have a pH in the range of about 6
to about 10 and/or are substantially isotonic. As described above
with regard to the presently useful antiseptic compositions, buffer
components and/or tonicity adjusting components and/or other
components may be included in the presently useful irrigating
compositions to provide such compositions have the desired pH
values and/or tonicities and/or other beneficial properties.
Although any suitable concentration of chlorine dioxide may be
included in the presently useful surgical irrigating compositions,
it is preferred that the chlorine dioxide be present in an amount
in the range of about 0.05 to about 10, more preferably about 0.1
to about 5 and still more preferably about 0.2 to 3, ppm by weight
of the composition.
The presently useful chlorine dioxide-containing surgical
irrigating compositions can be employed substantially as prior art
ophthalmic surgical irrigants have been used. The presently useful
chlorine dioxide compositions are effective ophthalmic surgical
irrigants, are ophthalmically acceptable and, in addition,
preferably are effective to disinfect the ocular surgical area with
which the composition comes in contact.
The present methods preferably further comprise producing the
chlorine dioxide-containing compositions from precursor
compositions including chlorine dioxide precursor components. More
preferably, this producing step occurs directly prior to the
administering steps of the present methods. In this manner, the
presently useful compositions can be produced when needed, and have
a consistent and well controlled potency (effectiveness) or
chemical make-up so as to be both effective as an ophthalmic
antiseptic or an ophthalmic surgical irrigant and ophthalmically
acceptable to avoid detrimentally affecting the eye being cared for
or the ocular area undergoing surgery.
The media, preferably liquid media, useful in the present invention
are selected to have no substantial detrimental effect on the eye
or ocular tissue being cared for or irrigated and to allow and even
facilitate the present eye care or ocular tissue irrigation. The
media are preferably aqueous-based. A particularly useful aqueous
liquid medium is that derived from saline, for example, a
conventional saline solution or a conventional buffered saline
solution. The aqueous media preferably have a pH in the range of
about 6 to about 10, more preferably about 6 to about 8. The media
preferably have ophthalmically acceptable tonicity levels, for
example, of at least about 200 mOsmol/kg, more preferably in the
range of about 200 to about 400 mOsmol/kg.
Included among the chlorine dioxide precursor components suitable
for use are those which are adapted to provide for controlled
formation of chlorine dioxide. Thus, such precursors allow chlorine
dioxide to be shipped and stored with minimum loss of
effectiveness. Chlorine dioxide is formed when needed and wanted,
for example, in a liquid medium used in the present methods.
Specific examples of chlorine dioxide precursor components include
metal chlorites, such as alkali metal and alkaline earth metal
chlorites. Technical grade sodium chlorite is a very useful
chlorine dioxide precursor component. Chlorine dioxide-containing
complexes, such as complexes of chlorine dioxide with carbonate,
chlorine dioxide with bicarbonate and mixtures thereof are also
included as chlorine dioxide precursor components. The exact
chemical composition of many chlorine dioxide precursor components,
for example, stabilized chlorine dioxide (SCD) and the chlorine
dioxide complexes, is not completely understood. The manufacture or
production of certain chlorine dioxide precursor components is
described in McNicholas U.S. Pat. No. 3,278,447, which is
incorporated in its entirety herein by reference. Specific examples
of useful SCD products include that sold under the trademark Dura
Klor by Rio Linda Chemical Company, Inc., and that sold under the
trademark Anthium Dioxide by International Dioxide, Inc. An
especially useful SCD is a product sold under the trademark
Purogene.RTM. by Bio-Cide International, Inc.
In general, the chlorine dioxide precursor component may be
included in a medium, preferably a liquid medium, at a
predetermined concentration, effective to produce the desired
chlorine dioxide-containing composition.
In one embodiment, the chlorine dioxide precursor component
includes a functionality selected from carbonate, borate, sulfate,
phosphate, and mixtures thereof.
The chlorine dioxide precursor components useful in the present
invention are those which form or produce chlorine dioxide in a
liquid medium in response to at least one factor, preferably in the
presence of an activator or promoter component. The presently
useful compositions may further comprise an activator component in
an amount effective to effect formation of chlorine dioxide, for
example, an effective antiseptic amount or an effective
antimicrobial amount of chlorine dioxide, from the chlorine dioxide
precursor component.
Any suitable activator component may be employed to effect the
generation of chlorine dioxide from the presently useful chlorine
dioxide precursor components. Examples include, acidic materials to
increase the acidity of the medium, transition metal components,
oxygen-releasing components, organic acid anhydrides, chlorine
dioxide reducing components and the like. In addition, an
electrical current can be passed through a chlorine dioxide
precursor-containing liquid medium to effect formation of chlorine
dioxide.
Preferably, the composition used as an ophthalmic antiseptic or as
an irrigant in ocular surgical procedures is substantially free of
any activator (or other) component or residue thereof used to
promote, e.g., activate, the production of chlorine dioxide from
the chlorine dioxide precursor component. Thus, preferred activator
components are those which effectively promote the production of
chlorine dioxide without contaminating the final useful product.
This feature reduces the risks that the useful product is
irritating or otherwise harmful to the eye or ocular tissue being
cared for or irrigated. Particularly useful activator components
include such components which are present in a material phase,
e.g., a solid phase, which is separate from the material phase,
e.g., a liquid phase, containing the chlorine dioxide precursor
component. In this manner, the activator component can be
maintained separate from the resulting chlorine dioxide-containing
composition. Very useful activator components include solid
transition metal components.
At mildly acidic conditions, in particular at a pH of less than
about 6 and especially in the range of about 3 to about 5, the
production of chlorine dioxide is effected from the chlorine
dioxide precursors. Any suitable acidic component may be employed
as the activator component. The primary criteria for such acidic
component is that it have the ability to increase the acidity of
the liquid medium containing chlorine dioxide precursor
sufficiently to effect formation of chlorine dioxide from such
chlorine dioxide precursor, and preferably sufficiently to effect
formation of antiseptic amounts or disinfecting amounts of chlorine
dioxide from the presently useful chlorine dioxide precursors. Such
acidic components should also have no substantial detrimental
effect on the eye or ocular tissue being cared for or
irrigated.
Examples of the presently useful acidic components include mineral
acids, salts of such mineral acids, carboxylic acids, salts of such
carboxylic acids and mixtures thereof. The mineral acids include,
for example, citric acid, sulfuric acid, hydrogen halides,
phosphoric acid and the like. The carboxylic acids include both
mono- and poly-, e.g., di-, tri- and the like, carboxylic acids,
and preferably include 1 to about 10 carbon atoms per molecule. One
or more non-hydrocarbonaceous groups, e.g., hydroxy groups, halide
groups and the like, may be appended to the carboxylic acid. If any
acid salt is employed, it is preferred that the salt be an alkali
or alkaline earth metal salt, more preferably an alkali metal salt.
A particularly useful group of acidic components is selected from
alkali metal hydrogen phosphates, citric acid, lactic acid,
tartaric acid and mixtures thereof.
During chlorine dioxide generation using acid activation, it is
preferred that the liquid aqueous medium have a pH of about 6 or
less, in particular in the range of about 3 to about 5. The amount
of acidic component employed is preferably sufficient to provide
the precursor-containing liquid medium with the desired pH.
Any transition metal component capable of effecting the formation
of chlorine dioxide from a chlorine dioxide precursor in an aqueous
liquid medium, preferably at a pH between about 6 and about 10, or
possibly higher, may be employed as the activator component. The
primary criteria for such transition metal component is that it
have the ability to effect formation of chlorine dioxide from a
chlorine dioxide precursor. Such metal components should also have
no substantial detrimental effect on the eye or ocular tissue being
cared for or irrigated.
It is preferred that the activator component be present as a solid,
for example, to avoid contaminating the final useful product with
the activator or residue thereof. In certain embodiments, solid
metals can be easily and conveniently introduced into or removed
from the chlorine dioxide precursor-containing medium, as desired.
The activator, for example, metal, component may be immobilized, or
maintained substantially stationary, relative to the
precursor-containing medium.
The particular metals of interest herein are the transition metals
and mixture thereof, in particular from Group III metals, Group IV
metals, Group V metals, Group VI metals, Group VII metals, Group
VIII metals and mixture thereof.
Because of their high degree of effectiveness, platinum group
metals and mixtures thereof, and especially platinum or palladium,
are particularly useful. The platinum group metals include
platinum, palladium, iridium, ruthenium, rhodium and osmium.
The metal component or components may be present in the metallic
form and/or in a combined form as part of an organic or inorganic
compound or complex.
The amount of metal component needed to practice this invention is
to be viewed in terms of what quantity or surface area is useful to
generate a particular concentration of chlorine dioxide in a given
time and in light of the amount of precursor present in
solution.
Oxygen-releasing components useful as activator components in the
present invention include both inorganic and organic peroxy
compounds.
In one embodiment, the oxygen-releasing components which may be
used in the present invention are water soluble inorganic slats
such as, for example, the sodium, potassium, calcium, magnesium,
lithium and ammonium salts of oxygen-releasing sulfur compounds,
such as, for example, the perthiosulfates (S.sub.2 O.sub.5.sup.-2),
the persulfates (SO.sub.5.sup.-2), the peroxysulfates, such as the
peroxymonosulfates (HSO.sub.5.sup.-1) and the peroxydisulfates
(S.sub.2 O.sub.8.sup.-2), and mixtures thereof.
A particularly preferred oxygen-releasing component is potassium
peroxymonosulfate (KHSO.sub.5) and the preferred form of this
component is the triple salt which is a combination of potassium
peroxymonosulfate (KHSO.sub.5), potassium hydrogen sulfate
(KHSO.sub.4) and potassium sulfate (K.sub.2 SO.sub.4). This
composition is an acidic, water soluble, oxygen releasing powder
which is odorless, white, granular, stable and free flowing. Other
alkali metal, e.g., sodium, and ammonium salts are also useful.
Among useful organic peroxy compounds are the aliphatic and
aromatic percarboxylic acids based on the radical ##STR1## Organic
peroxy compounds are preferably the aliphatic or aromatic
percarboxylic acids and their alkali metal and ammonium salts.
Examples of the aliphatic peracids include peracetic acid,
perpropionic acid, up to perlauric acid. The preferred peracids are
aromatic such as perbenzoic acid and nuclear substituted perbenzoic
acids, especially those having melting points above 50.degree. C.
Especially preferred is p-methoxyperbenzoic acid.
The amount of oxygen-releasing component employed should be such as
to be effective to effect formation of an effective amount of
chlorine dioxide in the chlorine dioxide precursor-containing
medium. The oxygen-releasing component is preferably present, for
example, during the chlorine dioxide production, in an amount in
the range of about 0.01 mole or less to about 1 mole or more per
mole of potential chlorine dioxide present as chlorine dioxide
precursor in the medium. Particularly useful results are achieved
using oxygen releasing component in the range of about 0.01 mole to
about 0.1 mole per mole of potential chlorine dioxide present as
chlorine dioxide precursor in the medium.
In one embodiment, the activator component comprises an organic
acid anhydride component in an amount sufficient to effect
formation of chlorine dioxide from the precursor.
Any suitable organic acid anhydride component may be employed. The
primary criteria for such component is that it have the ability to
effect formation or generation of chlorine dioxide from the
chlorine dioxide precursor component in the medium. Such organic
acid anhydride components should also have no substantial
detrimental effect on the eye or ocular tissue being cared for or
irrigated.
Examples of useful organic acid anhydride components include
succinic anhydride, glutaric anhydride, maleic anhydride and the
like and mixtures thereof. The organic acid anhydride or anhydrides
are preferably present during the chlorine dioxide producing step
in an amount in the range of about 0.01 mole or less to about 1
mole or more per mole of potential chlorine dioxide present as
chlorine dioxide precursor.
Any suitable chlorine dioxide reducing component may be used as an
activator component in the present invention, provided that it
functions as described herein and has no substantial detrimental
effect, for example, on the eye or ocular tissue being cared for or
irrigated. Examples of useful chlorine dioxide reducing components
include, but are not limited to, sulfur-containing components, such
as SH (group)--containing water soluble lower alcohols,
dithiothreitol, bisulfites, thio urea, beta-mercaptoethanol,
2-mercaptopropionic acid, 2-mercapto-propionylglycine,
2-mercaptoethylaminehydrochloide, dithioerythritol, sulfites,
pyrosulfites, thiosulfates, dithionites, glutathione and the like;
N-acetylcysteine; acetylcysteine; cysteine hydrochloride ethyl
ester; homocysteine; carbamoylcysteine; cysteine; cysteine
hydrochloride; cysteinyl calycine; and the like and mixtures
thereof. A particularly useful chlorine dioxide reducing component
is selected from thiosulfates, for example, alkali metal
thiosulfates and hydrogen thiosulfate and mixtures thereof.
The amount of chlorine dioxide reducing component employed should
be such as to be effective to effect formation of chlorine dioxide,
in a chlorine dioxide precursor-containing medium in which the
chlorine dioxide reducing component is located. The chlorine
dioxide reducing component is preferably present in an amount less
than that amount effective to reduce all the potential chlorine
dioxide formable from the chlorine dioxide precursor in the liquid
medium. The chlorine dioxide reducing component may be present in
an amount in the range of about 0.01 mole or less to about 0.5 mole
or more per mole of potential chlorine dioxide present as chlorine
dioxide precursor in the medium. Particularly useful results are
achieved using amounts of chlorine dioxide reducing component in
the range of about 0.01 mole to about 0.1 mole per mole of
potential chlorine dioxide present as chlorine dioxide precursor in
the medium.
The following non-limiting examples illustrate certain features of
the present invention.
EXAMPLE 1
A conventional borate-buffered saline solution is selected. To this
solution is added a stabilized chlorine dioxide product (a chlorine
dioxide precursor), sold by Bio-Cide International Inc. under the
trademark PUROGENE.RTM.. The amount of stabilized chlorine dioxide
product added is sufficient to produce 5 ppm (by weight) of
chlorine dioxide in the solution if all the stabilized chlorine
dioxide product is converted to chlorine dioxide. The resulting
solution has a pH of about 7.3, is substantially isotonic, and is
ophthalmically acceptable.
A dispensing bottle is provided which includes a reservoir in which
50 ml of the above-noted solution is located. This bottle also
includes an outlet tip through which the solution must pass when
exiting the bottle. Located in this outlet tip are polyethylene
beads on which palladium is deposited. The beads contain about
0.01% by weight palladium.
The palladium-containing polyethylene beads are present in an
amount so that upon tipping the dispensing bottle upside down drops
of the above-noted solution pass over the beads and exit the
bottle. By passing over the beads, a portion of the stabilized
chlorine dioxide product is converted to chlorine dioxide so that
the solution exiting the bottle contains 2.5 ppm by weight of
chlorine dioxide.
A human patient having bacterial conjunctivitis in both eyes uses
the solution in the dispensing bottle as follows. Three times
daily, the patient places three drops of the above-noted chlorine
dioxide-containing solution directly from the dispensing bottle
into each eye. The chlorine dioxide-containing solution has no
detrimental effect on the eyes. In particular, no irritation or
discomfort is apparent from using this solution. After a period of
time, for example, in the range of about 3 to 5 days, the bacterial
conjunctivitis is substantially alleviated as a result of placing
the chlorine dioxide-containing solution in the eyes.
The above-noted procedure is continued until the bacterial
infection is completely resolved.
EXAMPLE 2
A larger quantity of the above-noted stabilized chlorine dioxide
product-containing borate buffered saline solution is prepared.
This solution is sterilized.
A surgical procedure to remove the diseased natural lens from a
human eye is conducted. As part of this surgical procedure, a
liquid is used to irrigate the ocular tissue effected by the
surgery, for example, to aid in the removal of the lens.
Approximately 1000 ml of the above-noted stabilized chlorine
dioxide product-containing solution is passed over polyethylene
beads on which palladium (0.01% by weight) is deposited. This
causes a portion of the stabilized chlorine dioxide product to be
converted to chlorine dioxide. A chlorine dioxide-containing
solution containing 2.5 ppm by weight of chlorine dioxide is
produced and is collected in a sterile container ready for use as a
surgical irrigant. This chlorine dioxide-containing solution is
used as an irrigant in the lens removal surgical procedure.
It is found that the solution is effective as a surgical irrigant.
Further, the ocular tissue which comes in contact with this
chlorine dioxide-containing irrigating solution is not
detrimentally affected by this solution. In addition, because of
the chlorine dioxide present in the solution, the ocular surgical
area which comes in contact with the irrigant is effectively
disinfected, thus reducing the risk of post-surgical infection.
While this invention has been described with respect to various
specific examples and embodiments, it is to be understood that the
invention is not limited thereto and that it can be variously
practiced within the scope of the following claims.
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